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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 127 records · Page 7Linked to original sources
PubMed1998

Psychophysiological analysis of mental load during driving on rural roads--a quasi-experimental field study.

The objective of this study was the development and validation of an integrated measure-assessment approach (driving performance and psychophysiological indicators) for the assessment of driving demands of rural road segments as a starting point for design. With 31 student test drivers and a selection of six study roads, the reactivity of psychophysiological parameters was evaluated based on a general model of cognitive-energetic effort regulation according to Hockey (1993). The road curvature change rate was introduced as the independent variable, which served as a criterion of objective road difficulty. Based on a reliability analysis, the longitudinal and cross-sectional stability, especially for heart rate (HR) and blink rate (BR) measures, is sufficiently high. Both these psychophysiological variables and speed vary as a function of the curvature change rate of the rural road segments. The speed parameter differentiates very strongly the different curvature change rates. Among the psychophysiological indicators, changes in the blink rate almost exactly mirror the level of the curvature change rate owing to the fact that the BR decreases almost steadily with increasing curvature change rate. Cardiovascular parameters, such as heart rate (HR) and heart rate variability (HRV), and skin conductance response (SCR) also vary in relation to driving difficulty of road segments, but at levels of intermediate curvature other additional road characteristics may also influence these measures.

Adult↗
PubMed1998

HLA-B*27 typing by group-specific hybridization in microtiter plates.

We have developed and evaluated a test for HLA-B*27 based on PCR and DNA hybridization in microtiter plates. A region within exon 2 of the HLA-B gene is amplified and labeled by PCR and the amplification product is hybridized to a group-specific HLA-B*27 and a generic control oligonucleotide probe in two separate cavities of the plate. Bound sequences are detected using an ELISA-like protocol. The assay has been evaluated on 254 DNA samples routinely received for B27 testing in parallel with serological and SSP-PCR typing. Results were concordant in typing 102 HLA-B27-positive and 152 HLA-B27-negative individuals except for two samples containing HLA-B*73, which stained B27 positive in the microwell test. The new procedure is rapid and simple to perform, and the microwell format is particularly suitable for automation.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Virtual DNA analysis--a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results.

In order to obtain reliable information on HLA types, DNA typing with sequence-specific oligonucleotide/primer (SSO/SSP) typing sets or sequencing-based typing (SBT) is increasingly performed. The quality of the evaluation depends on the presence of a complete listing of all typed alleles as well as on the ability of detecting all corresponding alleles/allele pairs. We have developed the concept of virtual DNA analysis (VDA), which is able to combine all types of SSO/SSP/SBT results and evaluate this typing in combination according to the latest published allele sequence lists. The concept is based on the target DNA recognised by the respective typing techniques. All SSO/SSP or SBT results are transformed to a virtual sample DNA, which subsequently is analysed. Evaluation of generic or allele-specific DNA typing or the combination of both is supported. Due to this flexible approach, all kinds of SSO/SSP sets, as far as the respective SSO/SSP sequences are available, can be entered and evaluated immediately. The combination of collected data of different typing sets and procedures leads to the highest possible typing resolution. If more than one possible allele combination persists, the program reduces the result to the most specific common denominator in a stepwise manner. VDA offers the possibility of re-evaluation of former SSO/SSP/SBT results, alone or in combination. No solutions are omitted. This might be a first step towards standardisation of evaluating DNA-based HLA typing results or transfer of the respective typing data for later evaluation.

Databases, Factual↗
PubMed1998

[Sentinel lymph nodes in breast carcinoma].

Aim of the experiment is to select patients with positive axillary lymph nodes by means of the sentinel lymph node concept. In this way all other patients who would not benefit from a lymph node dissection are spared from this procedure and its morbidity. Till now the sentinel lymphadenectomy is, however, still an experimental technic with yet unproven utility.

Axilla↗
PubMed1998

Prenatal diagnosis of a transient myeloproliferative disorder in trisomy 21.

We report the prenatal diagnosis of a transient myeloproliferative disorder suggestive of leukaemia in a fetus with hepatosplenomegaly, hydrops and 47, XY, +21 karyotype. The initial fetal white blood cell count at 26 + 5 weeks' gestation was 190/nl with 70 per cent blast cells. Immunophenotyping of the large blasts revealed surface markers suggestive of an early stem cell differentiation arrest resulting in undifferentiated polyclonal myelopoiesis. The fetal heart tracing showed minimal beat-to-beat variability in the presence of high leukocyte counts. Serial fetal blood sampling showed decreasing blast cells in the peripheral blood and normalization of white blood cell counts. Although there was increasing hydrops, this period was marked by improvement of the fetal heart rate pattern. Finally the fetus developed pancytopenia with increasing hydrops, AV-valvular insufficiency and venous Doppler studies indicative of cardiac decompensation prior to intra-uterine death at 31 + 5 weeks' gestation. Post-mortem examination revealed marked liver and splenic necrosis without evidence of residual leukaemic infiltration in any organ. Fetal hydrops and hepatosplenomegaly may indicate an underlying haematopoietic disorder warranting further investigation. Furthermore, this case indicates that transient abnormal myelopoesis may result in a fulminant clinical picture much like true leukaemia. This may be due to increased vulnerability of the fetus or represent a disease mechanism unique to fetuses with chromosomal abnormalities.

Adult↗
PubMed1997

Structure and erythroid cell-restricted expression of a chicken cDNA encoding a novel zinc finger protein of the Cys + His class.

We report the cloning, sequence analysis and expression pattern of chGfi, a zinc finger protein (Zfp)-encoding cDNA that was isolated from a cDNA library constructed with RNA from avian erythroblastosis virus (AEV)-transformed primary chicken erythroblasts. The 1387-bp-long chGfi cDNA encodes a full-length 337-amino-acid (aa) protein that contains six zinc fingers (Zf) of the 2Cys + 2His class at its C-terminus. Immunoblotting experiments with extracts from bone marrow cells detected a 38-kDa protein that corresponds to the M(r) of 38,690 calculated for the protein deduced from chGfi. The chGfi protein is most homologous to the rat Gfi-1 showing a sequence similarity of 92% over the Zf region and only two exchanges within the N-terminal 19 aa that constitute the Gfi-1 repressor domain. Expression of chGfi is only detected in transformed primary erythroblasts, in erythroid cells of the primitive and definitive lineage and in bone marrow cells. chGfi activity does not vary significantly during differentiation of transformed primary erythroblasts of the definitive lineage. No chGfi expression is detected in cells of the myeloid and lymphoid lineages or in a total of nine different organs of adult origin. Our results indicate that chGfi expression is restricted to erythroid cells of the primitive and definitive lineage.

Amino Acid Sequence↗
PubMed1997

Ifosfamide cytotoxicity on human tumor and renal cells: role of chloroacetaldehyde in comparison to 4-hydroxyifosfamide.

The initial metabolism of ifosfamide (IFO) consists of two different pathways, which lead to the alkylating metabolite 4-hydroxy-IFO and to chloroacetaldehyde (CAA). CAA has been reported to cause side effects, such as neuro- and nephrotoxicity, whereas no direct antitumor effect has been described thus far. Therefore, two human tumor cell lines (MXI and S117) and a renal tubular cell line (Landa Leiden) were exposed to 4-hydroxy-IFO, CAA, and a combination of both. The concentrations used were in the same range as measured in the blood of 10 patients treated with 5 g/m2 IFO. The cell survival was measured using the MTT assay. Similar dose-response curves were found for both metabolites. For the MX1 tumor, the IC50s of 4-hydroxy-IFO and CAA were 10.8 and 8.6 microM, respectively. For the reduction of S117 cell survival, higher concentrations of the metabolites were needed (25.0 microM 4-hydroxy-IFO and 15.3 microM CAA). Combination treatment of the cells resulted in an approximately additive effect. Both metabolites exhibited similar toxicity against Landa Leiden cells. Our results indicate that CAA has its own cytotoxic profile against tumor cells. Hence, we conclude that the molecular mechanism of action of IFO seems to be only in part an alkylating effect and that CAA may play an important role in the therapeutic efficacy of IFO.

Acetaldehyde↗
PubMed1997

Localisation of cardiac GS alpha in transgenic mice overexpressing GS alpha.

The biochemical and physiological effects of GS alpha activation are well known; however, little is known about the anatomical localisation of GS alpha in the myocardium. Knowledge of the localisation might yield insights into G protein function in heart. The utility of immunocytochemistry using immunofluorescent methods is limited in normal hearts because of the low expression of GS alpha. In order to magnify the GS alpha signal, we studied transgenic mice overexpressing myocardial GS alpha. Immunofluorescent techniques with confocal imaging using rabbit antiserum specific for GS alpha were studied in frozen sections of mouse left ventricle. GS alpha labeling appeared to be localised to the T-tubules and intercalated disks in the GS alpha overexpressing mouse hearts, whereas the control mice showed background fluorescence with diffuse faint labeling. The localisation of GS alpha to structures involved in calcium handling and membrane conductance places GS alpha at a focal point in the regulation of these key functions.

Animals↗
PubMed1997

[Breast carcinoma staging with sentinel lymphadenectomy].

The objective of our trial was to evaluate the significance and usefulness of sentinel lymphadenectomy (SLNE) for the staging of regional lymph nodes in breast cancer patients. The study presented illustrates the method and our results. As has been documented for melanoma, the first lymph node [sentinel node (SLN)] to receive lymphatic drainage from a primary tumor is the expected first site of lymph-node metastasis. The database presented includes 12 patients with operable breast cancer and clinically negative lymph nodes. In 11 cases the described method was applicable. In only one case was there no correlation between the histology of the SLN and the axillary specimen. Three SLN were tumor-positive. Successful completion of examination of a large number of patients with a long follow-up has the potential of reducing the number of axillary dissections and of significantly reducing morbidity in the majority of breast cancer patients.

Aged↗
PubMed1997

[Isolated histiocytosis X as rare differential diagnosis of indistinguishable neck lymph node swelling. A case report].

Cervical lymphadenopathies are widespread diseases in otorhinolaryngology. There are many differential diagnoses which have to be considered when swelling persists. To gain further information it is advisable to perform sonographically controlled fine needle aspiration biopsy (FNP). If there is no reliable result, it is necessary to remove a lymph node. We report on the rare case of isolated histiocytosis X in lymph nodes. A 63-year-old male had noticed a swelling of the right side of the neck about 6 weeks previously. The preliminary examinations (FNP/blood examinations) revealed no pathological findings. Only the histological examination delivered the diagnosis of histiocytosis X. Systemic manifestation was excluded by staging examinations. No further therapy was necessary after lymph node extirpation. The report demonstrates how to diagnose and treat this rare disease.

Biopsy↗
PubMed1997

Urinary excretion of ifosfamide, 4-hydroxyifosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy.

The oxazaphosphorine antineoplastic ifosfamide (IF) is metabolized by two different initial pathways: ring oxidation ("activation"), forming 4-OH-IF ("activated IF"), and side-chain oxidation with liberation of chloroacetaldehyde (CAA), forming the inactive metabolites 3-dechloroethylifosfamide or 2-dechloroethylifosfamide (3-DCE-IF, 2-DCE-IF). 4-OH-IF and 4-OH-IF-derived acrolein are thought to be responsible for IF-induced urotoxicity (hemorrhagic cystitis), whereas CAA may be involved in IF-associated nephrotoxicity (renal tubular damage). The thiol compound 2-mercaptoethane sulfonate sodium (mesna) has proved to inactivate sufficiently the urotoxic metabolites of oxazaphosphorine cytostatics and is therefore routinely given to patients receiving IF chemotherapy. The cumulative urinary excretion of IF, 4-OH-IF, 3-DCE-IF, 2-DCE-IF, mesna, and its disulfide dimesna was studied in 11 patients with bronchogenic carcinoma receiving IF on a 5-day divided-dose schedule (1.5 g/m2 daily) with concomitant application of mesna (0.3 g/m2 at 0,4, and 8 h after IF infusion). On day 1 the mean cumulative 24-h urinary recoveries (percentage of the IF dose) recorded for IF, 4-OH-IF, 3-DCE-IF, and 2-DCE-IF were 13.9%, 0.52%, 4.8%, and 1.5%, respectively. On day 5 the corresponding values were 12.2%, 0.74%, 9.9%, and 3.6%, respectively. This time-dependent increase in urinary excretion of IF metabolites, which is caused by rapid autoinduction of hepatic oxidative metabolism, may result in a higher probability for the development of urotoxic and nephrotoxic side effects during prolonged IF application. The mean 24-h urinary recoveries (percentage of the daily mesna dose) recorded for mesna/dimesna on day 1 (day 5) were 23.8%/45.2% (21.2%/39.8%), respectively. The mean molar excess of urinary reduced ("free") mesna over 4-OH-IF ranged from 11 to 72 on day 1 and from 6 to 40 on day 5. This indicates that although urinary excretion of 4-OH-IF rises with repeated IF application, mesna in standard doses should sufficiently inactivate the urotoxic IF metabolites.

Adult↗
PubMed1997

Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes.

Substances acting upon rapid eye movement (REM) sleep or paradoxical sleep (PS) can affect the number and/or the duration of PS episodes. In the present study, we investigated the effects of the proopiomelanocortin-derived peptide CLIP (corticotropin-like intermediate lobe peptide, ACTH 18-39) and its N-terminal fragments ACTH 18-24 and ACTH 20-24 on the duration of PS episodes in rats. Intracerebroventricular injection of ACTH 20-24 caused a pronounced prolongation of PS episodes (up to 7 min duration, never seen under baseline conditions), whereas ACTH 18-24 acted in a similar way but without reaching statistical significance. We suggest that short N-terminal CLIP fragment(s) may represent endogenous hypnogenic factor(s) involved in the regulation of paradoxical sleep.

Adrenocorticotropic Hormone↗
PubMed1997

Detection and differentiation of platelet-specific antibodies by flow cytometry: the bead-mediated platelet assay.

BACKGROUND: Platelet-reactive antibodies cause a number of clinical disorders. The detection and differentiation of these antibodies are prerequisites for the adequate treatment of these disorders. The bead-mediated platelet assay described here enables the detection and differentiation of platelet-bound antibodies by the use of flow cytometry. STUDY DESIGN AND METHODS: The bead-mediated platelet assay is based on the isolation of human platelet glycoproteins by using flow cytometric standardization beads after the incubation of typed platelets with human sera. The specificity and sensitivity of this assay were tested with five sera, each containing a known platelet-reactive antibody. The monoclonal antibody-specific immobilization of platelet antigens assay was used as a reference test. RESULTS: The bead-mediated platelet assay was able to determine the glycoprotein specificity of the antibody without cross-reactions in every case. In serial dilution tests, the bead-mediated platelet assay was able to detect the antibodies at higher dilutions than the monoclonal antibody-specific immobilization of platelet antigen assay. Total test time was 3.5 hours. CONCLUSION: The bead-mediated platelet assay is a fast and reliable method for the detection and differentiation of platelet-reactive antibodies.

Antibodies, Monoclonal↗
PubMed1997

[Does the core biopsy of solid liver lesions permit an exact histological classification? Results of a prospective study under routine clinical conditions].

PURPOSE: The aim of this prospective study was to answer the question to what extent percutaneous core-cut biopsy of solid lesions of the liver can permit (sub-)classification under routine conditions. MATERIAL AND METHODS: Subject of this study were 80 percutaneous core-cut biopsies of solid liver lesions in 75 patients. The biopsies were done consecutively under routine conditions by 10 different radiologists with Tru-Cut-needles and a biopsy gun with sonographic (n = 73) or CT (n = 7) guidance. After receiving the histological analysis, the radiologists then prospectively divided the biopsies into "valid" und "unclear" using clinical and radiologic data of the respective patient. The results were verified by a second biopsy, follow-up or surgery. RESULTS: 80% of all histological analyses were rated as "valid", 20% as "unclear". The accuracy of the "valid" reports in respect of ranking was 95% and 90% for the accurate tumour classification. These values were reduced to 81.3% and 74%, respectively, with regard to the total number of cases. The negative predictive value was reduced from 78% to 51.7%. CONCLUSION: Core-cut biopsy of solid liver lesions guided by imaging yields good results even under routine conditions as long as all histological reports have been correlated with imaging and clinical informations.

Biopsy, Needle↗
PubMed1997

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.

Child↗